Exercise Echocardiography or Exercise SPECT Imaging? - Core

Clinical Cardiology

Exercise Echocardiography or Exercise SPECT Imaging? A Meta-analysis of Diagnostic Test Performance Kirsten E. Fleischmann, MD, MPH; Maria G. M. Hunink, MD, PhD; Karen M. Kuntz, ScD; Pamela S. Douglas, MD

Context.—Cardiac imaging has advanced rapidly, providing clinicians with several choices for evaluating patients with suspected coronary artery disease, but few studies compare modalities directly. Objectives.—To review the contemporary literature and to compare the diagnostic performance of exercise echocardiography (ECHO) and exercise singlephoton emission computed tomography (SPECT) imaging in the diagnosis of coronary artery disease. Data Sources.—Studies published between January 1990 and October 1997 identified from MEDLINE search; bibliographies of reviews and original articles; and suggestions from experts in each area. Study Selection.—Articles were included if they discussed exercise ECHO and/or exercise SPECT imaging with thallous chloride TI 201 (thallium) or technetium Tc 99m sestamibi for detection and/or evaluation of coronary artery disease, if data on coronary angiography were presented as the reference test, and if the absolute numbers of true-positive, false-negative, true-negative, and false-positive observations were available or derivable from the data presented. Studies performed exclusively in patients after myocardial infarction, after percutaneous transluminal coronary angioplasty, after coronary artery bypass grafting, or with recent unstable coronary syndromes were excluded. Data Extraction.—Clinical variables, technical factors, and test performance were independently extracted by 2 reviewers on a standardized spreadsheet. Discrepancies were resolved by consensus. Results.—Forty-four articles met inclusion criteria. In pooled data weighted by the sample size of each study, exercise ECHO had a sensitivity of 85% (95% confidence interval [CI], 83%-87%) with a specificity of 77% (95% CI, 74%-80%). Exercise SPECT yielded a similar sensitivity of 87% (95% CI, 86%-88%) but a lower specificity of 64% (95% CI, 60%-68%). In a summary receiver operating characteristic model comparing exercise ECHO performance to exercise SPECT, exercise ECHO was associated with significantly better discriminatory power (parameter estimate, 1.18; 95% CI, 0.71-1.65), when adjusted for age, publication year, and a setting including known coronary artery disease for SPECT studies. In models comparing the discriminatory abilities of exercise ECHO and exercise SPECT vs exercise testing without imaging, both ECHO and SPECT performed significantly better than exercise testing. The incremental improvement in performance was greater for ECHO (3.43; 95% CI, 2.74-4.11) than for SPECT (1.49; 95% CI, 0.91-2.08). Conclusions.—Exercise ECHO and exercise SPECT have similar sensitivities for the detection of coronary artery disease, but exercise ECHO has better specificity and, therefore, higher overall discriminatory capabilities as used in contemporary practice. JAMA. 1998;280:913-920

JAMA, September 9, 1998—Vol 280, No. 10

CORONARY ARTERY disease is the leading cause of death in men and women in the United States.1 Methods of detecting and assessing the presence and extent of disease have become increasingly important in applying therapies to decrease morbidity and mortality.2 Exercise electrocardiography (ECG) is widely used for noninvasive detection of coronary artery disease due to its ready availability and relatively low cost, but imaging techniques such as myocardial perfusion scintigraphy or echocardiography (ECHO) are often added to improve detection and/or localization of exercise-induced ischemia or in patients in whom the ECG is uninterpretable. The choice between these 2 imaging modalities should rest in large part with a comparison of their diagnostic accuracy based on an aggregate of the available experience. Limited data are available comparing the performance of exercise single-photon emission computed tomography (SPECT) imaging and exercise ECHO directly,3-8 in that studies evaluated modest numbers of patients or were conducted by physicians and centers more expert in one technique than the other. Interpretation of the literature

From the Cardiology Division, University of California, San Francisco, Medical Center, San Francisco (Dr Fleischmann); and the Section for Clinical Epidemiology (Dr Kuntz), Brigham and Women’s Hospital, and the Cardiovascular Division (Dr Douglas), Beth Israel Deaconess Medical Center, Harvard Medical School, and the Department of Health Policy and Management (Drs Hunink and Kuntz), Harvard School of Public Health, Boston, Mass; and the Departments of Epidemiology and Biostatistics and Radiology, Erasmus University, Rotterdam, the Netherlands (Dr Hunink). Corresponding author: Kirsten E. Fleischmann, MD, MPH, Cardiovascular Division, University of California, San Francisco, Medical Center, 505 Parnassus Ave, San Francisco, CA 94143-0214 (e-mail: Fleischm@ cardio.ucsf.edu).

Meta-analysis of Exercise SPECT vs Exercise ECHO—Fleischmann et al

©1998 American Medical Association. All rights reserved.

913

overall has been hampered by significant variability in case mix and pretest probability of disease, differences in the positivity criteria used, and the lack of reliable techniques to combine reports on the performance of diagnostic tests.9 Therefore, we undertook a meta-analysis of the contemporary literature on exercise SPECT imaging and exercise ECHO using a new methodologic tool, summary receiver operating characteristic (SROC) analysis.10-12 METHODS Data Extraction A literature review was performed to identify articles published from January 1990 to October 1997 in the English-language literature on exercise SPECT imaging and exercise ECHO.12 We focused on this period because both exercise ECHO and exercise SPECT were in widespread clinical use. Also, these years postdated several potentially important developments in myocardial perfusion imaging, such as SPECT techniques and the introduction of technetium Tc 99m sestamibi as an imaging agent. Articles were obtained through a MEDLINE search using the key words coronary disease and exercise test in conjunction with either echocardiography, thallium or thallium radioisotopes, or sestamibi and restricted by the term human; from bibliographies of original and review articles; and in response to suggestions by experts in each area. Articles3-8,14-51 were included in the analysis if (1) exercise ECHO and/or exercise SPECT imaging were performed with thallous chloride Tl 201 (thallium) or technetium Tc 99m sestamibi to detect and/or evaluate coronary artery disease (if data on exercise ECG results in the same patient population were also presented, these data were extracted, although a comprehensive search of the literature concerning standard exercise testing was not performed); (2) data on coronary angiography were presented as the reference test; and (3) the absolute numbers of true-positive, false-negative, true-negative,andfalse-positiveobservations were available or derivable from the data presented. Studies performed exclusively in patients after myocardial infarction (MI), after percutaneous transluminal coronary angioplasty, after coronary artery bypass grafting (CABG), or with unstable coronary syndromes were excluded. One stress ECHO article was excluded because of its substantially different positivity criterion,13 namely displacement of the atrioventricular plane. In cases in which authors had published several reports in quick succession, we were able to contact them and to determine 914 JAMA, September 9, 1998—Vol 280, No. 10

whether multiple analyses were reported on a substantially overlapping patient population. If this was the case, only 1 report was used in the analysis to avoid undue influence by results in one cohort of patients. A radiologist (M.G.M.H.) and cardiologist (K.E.F.) independently extracted data on clinical variables, technical factors, and test performance by meansofastandardizedspreadsheet.Discrepancies were resolved by consensus. Variables extracted included identifying information (first author, journal, city, and institution), publication year, mean age, percentage of male patients, clinical indication or setting and percentage of patients with previous MI, percutaneous transluminal coronary angioplasty, or CABG surgery. In addition, we recorded such test factors as the test used, the type of exercise performed, type of radionuclide used (if applicable), the positivity criterion used, the reference test used, how authors defined significant coronary artery disease (eg, $50% stenosis or $70% stenosis), and the presence of possible verification bias. The number of patients with and without disease, number of true positives and false positives, and percentage of diagnostic tests (patients reached at least 85% of their predicted maximal heart rate) were extracted as well as the percentage of uninterpretable tests and morbidity and mortality associated with each test, if provided. If the article reported sensitivity and specificity data for important patient subsets, such as patients with multivessel disease, these data were extracted separately. If several types of tests were assessed in the same report (ie, exercise ECG, exercise ECHO, and exercise SPECT), data on test performance were extracted for each. An assessment of the likelihood of verification bias52 was made by noting whether the decision to proceed to the reference test, in this case contrast angiography, was in part dependent on the results of the noninvasive test. Since positive noninvasive test results are more likely to be followed up by an invasive test, this tends to increase the chance of detecting a true positive relative to a false negative and tends to increase the chance of detecting a false positive relative to a true negative. Therefore, sensitivity may appear falsely elevated and specificity falsely depressed in the verified sample. Weighted Pooled Analysis In our analysis, pooled results weighted by the sample size of each study were first calculated using a fixed-effects model.53 Pooled weighted results were also generated for important patient subsets, such as patients without prior MI and patients with severe coronary artery dis-

ease as defined in each report. We also explored the effect of varying positivity criteria on pooled results. For the analysis, positivity criteria were grouped according to whether an abnormal test result required that an abnormality manifested after exercise vs either at rest or after exercise. If not fully specified, a less stringent criterion of abnormality at rest or after exercise was used. In addition, exercise ECHO studies were grouped as requiring either new regional wall motion abnormalities (RWMAs) or new or worse RWMAs. All results are presented as percentage sensitivity and specificity with 95% confidence intervals (CIs). SROC Analysis for Each Diagnostic Test Receiver operating characteristic curves graphically represent the truepositive and false-positive ratios for a diagnostic test when the threshold for a positive test result is varied.54 The area under the curve summarizes the overall diagnostic performance of the test, with larger areas corresponding to a more discriminating test. An area of 0.5 corresponds to a test whose results are no better than chance, while an area of 1.0 denotes a perfect test. SROC analysis assumes that part of the variability in test performance reported in the literature is due to the use of different cut points or positivity criteria and adjusts for these differences. For example, a study of exercise ECHO may use a more stringent criterion such as development of a new RWMA to signal an abnormal test result or a more lenient criterion such as the absence of a hyperkinetic contractile response to exercise resulting in a different reported sensitivity and specificity. SROC analysis also allows adjustment for important clinical covariates and for comparison between different types of tests.55 In this last case, a variable corresponding to the type of exercise testing used (eg, exercise ECHO or exercise SPECT) is entered into the regression equation. The b-coefficients for the variable give a measure of the difference in diagnostic performance of the 2 tests, with positive coefficients indicating better discriminatory power and negative coefficients corresponding to reduced discriminatory ability. SROC curves were generated separately for each test. We assessed the influence of variables including publication year; proportion of patients with prior MI; indication or setting for the test; mean age; proportion of men in the study population; presence of verification bias; the angiographic definition of disease (50% stenosis vs 70% or 75%); type of exercise (treadmill vs other); positivity criterion; and in the case of exercise SPECT, type of nuclide (thallium



vs technetium Tc 99m sestamibi) and type of analysis (visual vs quantitative) on test performance. We used a significance level of P,.05, implying that b regression coefficients whose 95% CIs do not cross zero are statistically significant. Since multiple variables were tested, one would normally adjust P values for multiple comparisons, eg, with a Bonferroni correction. However, to minimize the chance of missing potential confounding factors, all explanatory variables with P ,.05 were included in subsequent multivariate analyses. The Bonferroni-adjusted P values in our analyses were approximately .005; therefore, explanatory variables with .005 , P , .05 should be interpreted with caution. Data for some explanatory variables were not specified in all articles. For example, the proportion of prior percutaneous transluminal coronary angioplasty and CABG and the percentage of uninterpretable tests were excluded from all analyses due to missing data. Also, in the 1 article in which mean age was not given, in the 1 case in which the proportion of men was absent, in the 1 article in which the clinical setting for testing was not fully specified, and in the 2 articles in which the proportion of patients with MI was not specified, we used estimates for these variables based on a best subset regression analysis, so the widest range of literature could be included. Sensitivity analyses using weighted mean values for the missing data or excluding these articles from the analysis did not change the results substantively. Therefore, the base case including all articles is presented. We then assessed which explanatory variables were significant in multivariate analysis for each test using stepwise forward regression analysis with backward elimination including all variables. All variables with a P,.05 were kept in the model. Variables with .05,P,.10 were kept in the model if they substantially increased the explanatory power of the model. Comparison SROC Analyses Between Diagnostic Tests SROC curves were performed comparing exercise ECHO to exercise SPECT, exercise ECHO to exercise ECG, and exercise SPECT to exercise ECG. In each case, all explanatory variables were once again tested along with the variable indicating the test comparison. We then performed multivariate stepwise forward regression with backward elimination including all variables with P,.05 in the step above as well as all variables significant in multivariate analysis for each individual test. To develop a parsimonious JAMA, September 9, 1998—Vol 280, No. 10

model with similar explanatory variables across all comparisons, we included in the final models significant variables with similar effects for all tests as well as interaction terms to account for significant variables with effects specific to a particular diagnostic test. Final models were tested for heterogeneity by comparing the values predicted by the model to the 95% CI of the actual values for each article. Similar SROC analyses were also performed in the following important subsets: studies comparing exercise ECHO and exercise SPECT directly in the same patients, patients without prior MI, and patients with severe disease as defined in each report. RESULTS Overview of Studies A total of 902 citations published between January 1990 and October 1997 were screened, and 44 articles met inclusion criteria.3-8,14-51 The clinical characteristics of the studies analyzed are outlined in Table 1. Overall, 24 studies reported exercise ECHO results in 2637 patients with a weighted mean age of 59 years. The patients were predominantly men (69%). Significant coronary artery disease, as defined in each report, was present in 66% of patients and prior MI was present in 20% of patients. Twentyseven studies reported exercise SPECT data on 3237 patients, of whom 70% were male, with a mean age of 59 years. Significant coronary artery disease was present in 78%, with past MI in 33%. In 24 articles on exercise ECHO and/or exercise SPECT, data on results of the exercise ECG in the same patient population were also given. These encompassed 2456 patients with a mean age of 59 years, of whom 66% were men. The prevalence of coronary artery disease was 69% with past MI in 20%. Weighted Pooled Results Diagnostic test performance for individual studies is outlined in Table 1. In pooled data weighted by the number of patients with and without disease in each study, exercise ECHO had a sensitivity (true-positive ratio) of 85% (95% CI, 83%87%) with a specificity (1 − false-positive ratio) of 77% (95% CI, 74%-80%). The SPECT analyses yielded a similar sensitivity of 87% (95% CI, 86%-88%) but a lower specificity of 64% (95% CI, 60%68%). Weighted pooled data for exercise ECG revealed a significantly lower sensitivity of 52% (95% CI, 50%-55%) and a specificity of 71% (95% CI, 68%-74%). When only patients without prior MI were considered, the sensitivity and specificity for exercise ECHO were similar to those of the cohort overall at 87%

(95% CI, 84%-89%) and 84% (95% CI, 81%-88%). Weighted pooled results for SPECT in this subset were also similar to overall results with a sensitivity of 86% (95% CI, 83%-88%) and a specificity of 62% (95% CI, 55%-70%). The criterion for severe disease varied from article to article but generally denoted multivessel disease. In patients with severe disease, the sensitivity for exercise ECHO rose to 92% (95% CI, 90%-94%) when any abnormal test result was considered positive, but the specificity also dropped significantly to 54% (95% CI, 50%-58%). In contrast, when only abnormalities in multiple coronary distributions were considered an abnormal test result, the sensitivity fell to 60% (95% CI, 53%-67%) while specificity rose to 88% (95% CI, 85%-92%). Similar trends were seen for exercise SPECT with a sensitivity of 92% (95% CI, 90%-94%) and a specificity of 21% (95% CI, 19%-24%) when any abnormality was considered a positive test result, but a sensitivity of 44% (95% CI, 38%-49%) and a specificity of 87% (95% CI, 85%-89%) when only abnormalities in multiple distributions were considered positive. Pooled results were analyzed by positivity criteria as outlined in the “Methods” section and compared with the overall results. No significant differences in sensitivity were detected for either exercise ECHO or exercise SPECT. However, specificity in reports requiring an abnormality seen only after exercise rather than at rest or after exercise was significantly higher for exercise SPECT (76% [95% CI, 69%-83%] vs 61% [95% CI, 57%-65%]) and for exercise ECHO (84% [95% CI, 81%-87%] vs 70% [95% CI, 66%-74%]). Specificity was also higher for exercise ECHO reports requiring a new RWMA than for those using a new or worsened RWMA as a positivity criterion (93% [95% CI, 88%98%) vs 75% [95% CI, 72%-78%]). SROC Analysis for Each Diagnostic Test In univariate analysis for exercise ECHO, age and publication year were significant predictors. The discriminatory power of the test diminished slightly with increasing mean age (b-coefficient, −0.22 per year; 95% CI, −0.31 to −0.12) and with later publication year ( −0.41 per year; 95% CI, −0.58 to −0.24). Performance was better in reports requiring an abnormality seen only after exercise rather than at rest or after exercise (0.87; 95% CI, 0.005-1.74). Sex was not a significant predictor (0.40; 95% CI, −0.99 to 1.79). Similarly, increasing age (−0.15; 95% CI, −0.24 to −0.06) was a significant predictor of SPECT performance. Unlike exercise ECHO, settings that in-



915

Table 1.—Clinical Characteristics of the Studies Included in the Meta-analysis* Age, Mean, Men, Previous y % MI, %

Reference ECHO only Beleslin et al35

Exercise Used

Exercise Radionuclide Verification ECG Used Bias Results

Positivity Criterion

True False True False Positive Negative Negative Positive

50

85

57

Treadmill

No

Yes

New or worse RWMA after exercise

105

14

14

3

Bjornstad et al36

58

81

59

Upright bicycle

No

Yes


26

5

4

2

Cohen et al37

63

98

25

Supine ergometry

No

Yes


29

8

13

2

Crouse et al38

62

67

0

Treadmill

Yes

Yes

Absence of hyperkinesis with exercise

170

5

34

19

Dagianti et al39

54

79

39

Supine ergometry

No

Yes


19

6

33

2

Galanti et al40

54

87

0

Bicycle

Likely

Yes

New RWMA after exercise

25

2

25

1

Jun et al41

54

83

17

Treadmill

Likely

Yes

Absence of hyperdynamic response after exercise

28

4

14

1

Luotolahti et al

55

85

48

Bicycle

No

Yes


101

7

7

3

Marangelli et al43

58

84

0

Treadmill

No

No

New RWMA after exercise

42

5

30

3

Marwick et al44

57

79

37

Treadmill

Yes

Yes

RWMA after exercise or at rest

96

18

31

5

Marwick et al45

60

0

0

Treadmill and bicycle

Yes

Yes

RWMA after exercise or at rest

47

12

83

19

Marwick et al46

58

59

0

Treadmill

No

No

Failure to augment or worsening wall motion

44

18

77

8

Roger et al47

64

77

26

Treadmill

...

Yes

No

Absence of hyperdynamic response after exercise

50

10

56

34

Roger et al48

64

100

0

Treadmill

...

Yes

Yes

RWMA at rest or after exercise

151

43

22

28

Roger et al48

66

0

0

Treadmill

...

Yes

Yes

RWMA at rest or after exercise

46

12

14

24

Ryan et al49

57

75

43

Bicycle

Yes

Yes

New or worse RWMA after exercise or at rest RWMA

193

18

76

22

Tawa et al50

58

70

45

Treadmill

Yes

Yes

Fixed or reversible RWMA

31

2

10

2

Williams et al51

60

0

0

Bicycle

No

Yes


29

4

31

6

SPECT only Berman et al14

64

73

0

Treadmill

MIBI/TI

Yes

No

Fixed or reversible PD involving 2 or more segments

50

5

6

2

Chae et al15

62

0

42

Treadmill

TI

Yes

Yes

PD at rest or after exercise

116

47

52

28

Christian et al16

63

77

42

Treadmill

TI

Likely

No

Fixed or reversible PD

527

51

30

80

Fleming et al17

55

60

43

Treadmill

MIBI

Likely

No

PD with stress

16

1

6

2

Gupta et al18

58

83

40

Treadmill

TI

Likely

No


62

14

14

3

Hambye et al19

60

70

0

Bicycle

MIBI

No

Yes


75

16

28

9

Heiba et al20

50

64

31

Treadmill

MIBI

Yes

No

PD not otherwise specified

28

2

2

2

Ho et al21

56

76

33

Bicycle

TI

No

No


29

9

10

3

Kiat et al22

56

74

45

Treadmill

MIBI

Likely

No


45

3

4

1

Mahmarian et al23

56

74

43

Treadmill

TI

Likely

No


192

29

65

10

Minoves et al24

57

...

42

Treadmill

MIBI/TI

Likely

No


27

3

22

2

Nguyen et al25

62

65

37

Treadmill

TI

No

No


19

6

5

0

Oguzhan et al26

51

84

30

Treadmill

MIBI

No

Yes

Reversible PD

47

2

15

6

Palmas et al27

60

81

30

Treadmill

MIBI

Likely

No

PD after exercise or at rest

60

6

3

1

Rubello et al28

51

88

57

Bicycle

MIBI

Likely

No

PD after exercise

100

7

8

5

Solot et al29

61

62

...

Bicycle

MIBI

Likely

No


87

3

27

11

Sylven et al30

58

63

37

Bicycle

MIBI

Yes

Yes

Persistent or transient PD

41

16

5

5

Taillefer et al31

58

0

17

Treadmill

MIBI

No

No

Reduced uptake at rest or after exercise

23

9

13

3

Van Train et al32

56

76

19

Treadmill

MIBI

Yes

No

PD after exercise

91

11

8

14

Van Train et al33

60

83

16

Treadmill

MIBI

Likely

No


28

1

4

5

Van Train et al34

...

86

35

Treadmill

TI

Likely

No


290

17

32

32

42

cluded known coronary artery disease vs suspected coronary artery disease only were associated with better discriminatory performance (1.14; 95% CI, 0.59-1.70) as were higher proportions of men in the 916 JAMA, September 9, 1998—Vol 280, No. 10

study population (1.89; 95% CI, 0.72-3.07). No predictors were significant for exercise ECG. In multivariate analysis, increasing age (−0.16; 95% CI, −0.23 to −0.09) re-

mained a significant predictor of performance for exercise ECHO, as did a setting including known coronary artery disease (−0.56; 95% CI, −1.00 to −0.12). For exercise SPECT, a setting including



Table 1.—Clinical Characteristics of the Studies Included in the Meta-analysis* (cont)

Reference ECHO and SPECT Hecht et al3

Hoffmann et al4

Marwick et al5

Pozzoli et al6

Quinones et al7

Salustri et al8

Mean Men, Previous Age, y % MI, % 58

57

59

52

57

59

86

24

77

0

70

87

67

80

0

19

...

36

Exercise Used Treadmill/ bicycle

Bicycle

Bicycle

Bicycle

Treadmill

Bicycle

Radionuclide Verification Used Bias

Exercise ECG Results

TI

Yes

MIBI

MIBI

MIBI

TI

MIBI/TI

No

No

Yes

No

Yes

Yes

Yes

Likely

Yes

No

Yes

Positivity Criterion

True False True False Positive Negative Negative Positive

New or worsening RWMA or severe RWMA at rest

46

5

16

4

SPECT PD on exercise or rest images

47

4

13

7

ECHO new RWMA after exercise

40

10

14

2

SPECT PD not otherwise specified

37

5

9

4

ECHO RWMA at rest or after exercise

49

7

24

6

SPECT fixed or reversible PD

41

15

21

9

ECHO new RWMA after exercise

35

14

25

1

SPECT partially or completely reversible PD after exercise

41

8

23

3

ECHO new or worse RWMA after exercise or RWMA at rest

64

22

23

3

SPECT fixed or reversible PD

65

21

21

5

ECHO new or worse RWMA after exercise or RWMA at rest

26

4

12

2

SPECT transient PD or PD at rest

25

5

9

5

*ECHO indicates echocardiography; SPECT, single-photon emission computed tomography; ECG, electrocardiography; MI, myocardial infarction; MIBI, technetium Tc 99m sestamibi; TI, thallous chloride TI 201 (thallium); RWMA, regional wall motion abnormality; and PD, perfusion defect. Ellipses indicate that data is not available.

known or suspected coronary artery disease (1.19; 95% CI, 0.67-1.70) in the study population was associated with improved performance. For both tests, performance diminished with later publication year with a parameter estimate of −0.27 (95% CI, −0.40 to −0.14) for ECHO and −0.15 (95% CI, −0.28 to −0.012) for SPECT. No explanatory variables were significant for exercise ECG in multivariate analysis.

Table 2.—Comparison SROC Analyses Between Diagnostic Tests*

Exercise SPECT vs exercise ECG

P ,.001

Age, per year

−0.12 (−0.17 to −0.06)

,.001

Publication year

−0.21 (−0.30 to −0.11)

,.001

0.77 (0.26 to 1.29) 1.49 (0.91 to 2.08)

.004 ,.001

SPECT mixed setting SPECT vs ETT Age, per year SPECT publication year

Exercise ECHO vs exercise ECG

Comparison SROC Analyses Between Diagnostic Tests

b-Coefficient† (95% CI) 1.18 (0.71 to 1.65)

Comparison Variable Exercise ECHO vs exercise SPECT ECHO vs SPECT

SPECT mixed setting ECHO vs ETT Age, per year

JAMA, September 9, 1998—Vol 280, No. 10

.05

−0.15 (−0.27 to −0.029)

.02

1.01 (0.52 to 1.50) 3.43 (2.74 to 4.11) −0.066 (−0.11 to −0.021)

ECHO publication year

In a model comparing exercise ECHO performance to SPECT, exercise ECHO displayed significantly better discriminatory power (parameter estimate for incremental improvement, 1.18; 95% CI, 0.71-1.65), when adjusted for age, publication year, and a setting including known coronary artery disease for SPECT studies (Table 2). In models comparing the performance of exercise ECHO vs exercise ECG and exercise SPECT vs exercise ECG, both ECHO and SPECT performed significantly better than exercise ECG (Table 2). The incremental improvement was greater for ECHO than for SPECT. These results are presented graphically in Figures 1 and 2. In the subset of reports (n=6) comparing exercise ECHO and exercise SPECT directly in the same patients, exercise

−0.047 (−0.093 to −0.0004)

−0.35 (−0.50 to −0.21)

Adjusted r2

0.64

0.67

,.001 ,.001 .005

0.78

,.001

*CI indicates confidence interval; ECHO, echocardiography; SPECT, single-photon emission computed tomography; ECG, electrocardiography; and ETT, exercise treadmill testing †The b-coefficient for the variable gives a measure of the difference in diagnostic performance of the 2 tests, with positive coefficients indicating better discriminatory power and negative coefficients corresponding to reduced discriminatory ability.

ECHO also displayed better discriminatory performance parameter estimate (1.06; 95% CI, 0.77-1.36) in a model adjusted for age. In patients without prior MI, results were qualitatively similar to the overall analysis. When exercise ECHO and exercise SPECT were compared in this subgroup, exercise ECHO had better discriminatory power (1.21; 95% CI, 0.57-1.85). Both exercise SPECT and exercise ECHO performed significantly better than exercise ECG in patients without prior MI, but the incremental improvement for exercise ECHO was

larger (2.35; 95% CI, 1.79-2.91) than for exercise SPECT (1.36; 95% CI, 0.582.15). Results were also similar for models assessing diagnostic performance in patients with severe coronary artery disease as defined by each report. Exercise ECHO performed significantly better than exercise SPECT (parameter estimate, 0.91; 95% CI, 0.26-1.56). This result should be interpreted with caution, however, given the varying definitions of severe coronary artery disease from study to study and the relatively few studies in which these data were reported.



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Base Case

Worst Case

Best Case

True-Positive Ratio

A

Studies With >100 Patients

B

C

1.0

1.0

1.0

0.8

0.8

0.8

0.6

0.6

0.6

0.4

0.4

0.4

0.2

0.2

0.2

0.0

0.2

0.4

0.6

0.8

1.0

False-Positive Ratio

0.0

Studies With